Concept development of a Mach 4 high-speed civil transport

A study was conducted to configure and analyze a 250 passenger, Mach 4 High Speed Civil Transport with a design range of 6500 n.mi. The design mission assumed an all-supersonic cruise segment and no community noise or sonic boom constraints. The study airplane was developed in order to examine the technology requirements for such a vehicle and to provide an unconstrained baseline from which to assess changes in technology levels, sonic boom limits, or community noise constraints in future studies. The propulsion, structure, and materials technologies utilized in the sizing of the study aircraft were assumed to represent a technology availability date of 2015. The study airplane was a derivative of a previously developed Mach 3 concept and utilized advanced afterburning turbojet engines and passive airframe thermal protection. Details of the configuration development, aerodynamic design, propulsion system, mass properties, and mission performance are presented. The study airplane was estimated to weigh approx. 866,000 lbs. Although an aircraft of this size is a marginally acceptable candidate to fit into the world airport infrastructure, it was concluded that the inclusion of community noise or sonic boom constraints would quickly cause the aircraft to grow beyond acceptable limits using the assumed technology levels

Detection of viable Mycobacterium ulcerans in clinical samples by a novel combined 16S rRNA reverse transcriptase/IS2404 real-time qPCR assay.

Detection of Viable <em>Mycobacterium ulcerans</em> in Clinical Samples by a Novel Combined 16S rRNA Reverse Transcriptase/IS<em>2404</em> Real-Time qPCR Assa

Infection with Mansonella perstans Nematodes in Buruli Ulcer Patients, Ghana.

During August 2010-December 2012, we conducted a study of patients in Ghana who had Buruli ulcer, caused by Mycobacterium ulcerans, and found that 23% were co-infected with Mansonella perstans nematodes; 13% of controls also had M. perstans infection. M. perstans co-infection should be considered in the diagnosis and treatment of Buruli ulcer

The Somatosensory Link in Fibromyalgia: Functional Connectivity of the Primary Somatosensory Cortex Is Altered by Sustained Pain and Is Associated With Clinical/Autonomic Dysfunction

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111091/1/art39043.pd

Electric Current Perturbation Calculations for Half-Penny Cracks

The electric current perturbation (ECP) method1–4 consists of inducing or injecting an electric current flow in the material to be examined and then detecting localized perturbations of the magnetic flux associated with current flow around material defects such as cracks or inclusions. Empirically, ECP data has shown strong correlations among certain signal features and crack size characteristics, and thus promises to be a useful method for quantitative NDE. To aid in the further development of the method, the objectives of the work reported in this paper are (1) to develop a mathematical model of the ECP flux distribution for a half-penny crack, (2) to determine the degree of validity of the model through comparisons with experimental data, and (3) to develop a detailed theory of sizing relationships for half-penny cracks

Microbiological, histological, immunological, and toxin response to antibiotic treatment in the mouse model of Mycobacterium ulcerans disease.

Mycobacterium ulcerans infection causes a neglected tropical disease known as Buruli ulcer that is now found in poor rural areas of West Africa in numbers that sometimes exceed those reported for another significant mycobacterial disease, leprosy, caused by M. leprae. Unique among mycobacterial diseases, M. ulcerans produces a plasmid-encoded toxin called mycolactone (ML), which is the principal virulence factor and destroys fat cells in subcutaneous tissue. Disease is typically first manifested by the appearance of a nodule that eventually ulcerates and the lesions may continue to spread over limbs or occasionally the trunk. The current standard treatment is 8 weeks of daily rifampin and injections of streptomycin (RS). The treatment kills bacilli and wounds gradually heal. Whether RS treatment actually stops mycolactone production before killing bacilli has been suggested by histopathological analyses of patient lesions. Using a mouse footpad model of M. ulcerans infection where the time of infection and development of lesions can be followed in a controlled manner before and after antibiotic treatment, we have evaluated the progress of infection by assessing bacterial numbers, mycolactone production, the immune response, and lesion histopathology at regular intervals after infection and after antibiotic therapy. We found that RS treatment rapidly reduced gross lesions, bacterial numbers, and ML production as assessed by cytotoxicity assays and mass spectrometric analysis. Histopathological analysis revealed that RS treatment maintained the association of the bacilli with (or within) host cells where they were destroyed whereas lack of treatment resulted in extracellular infection, destruction of host cells, and ultimately lesion ulceration. We propose that RS treatment promotes healing in the host by blocking mycolactone production, which favors the survival of host cells, and by killing M. ulcerans bacilli

Mycolactone Diffuses into the Peripheral Blood of Buruli Ulcer Patients - Implications for Diagnosis and Disease Monitoring.

BACKGROUND: Mycobacterium ulcerans, the causative agent of Buruli ulcer (BU), is unique among human pathogens in its capacity to produce a polyketide-derived macrolide called mycolactone, making this molecule an attractive candidate target for diagnosis and disease monitoring. Whether mycolactone diffuses from ulcerated lesions in clinically accessible samples and is modulated by antibiotic therapy remained to be established. METHODOLOGY/PRINCIPAL FINDING: Peripheral blood and ulcer exudates were sampled from patients at various stages of antibiotic therapy in Ghana and Ivory Coast. Total lipids were extracted from serum, white cell pellets and ulcer exudates with organic solvents. The presence of mycolactone in these extracts was then analyzed by a recently published, field-friendly method using thin layer chromatography and fluorescence detection. This approach did not allow us to detect mycolactone accurately, because of a high background due to co-extracted human lipids. We thus used a previously established approach based on high performance liquid chromatography coupled to mass spectrometry. By this means, we could identify structurally intact mycolactone in ulcer exudates and serum of patients, and evaluate the impact of antibiotic treatment on the concentration of mycolactone. CONCLUSIONS/SIGNIFICANCE: Our study provides the proof of concept that assays based on mycolactone detection in serum and ulcer exudates can form the basis of BU diagnostic tests. However, the identification of mycolactone required a technology that is not compatible with field conditions and point-of-care assays for mycolactone detection remain to be worked out. Notably, we found mycolactone in ulcer exudates harvested at the end of antibiotic therapy, suggesting that the toxin is eliminated by BU patients at a slow rate. Our results also indicated that mycolactone titres in the serum may reflect a positive response to antibiotics, a possibility that it will be interesting to examine further through longitudinal studies

Kinetics of mycolactone in human subcutaneous tissue during antibiotic therapy for Mycobacterium ulcerans disease.

BACKGROUND: Mycobacterium ulcerans (M. ulcerans) causes a devastating necrotising infection of skin tissue leading to progressive ulceration. M. ulcerans is the only human pathogen that secretes mycolactone, a polyketide molecule with potent cytotoxic and immunomodulatory properties. These unique features make mycolactone an attractive biomarker for M. ulcerans disease. We sought to measure the concentration of mycolactone within lesions of patients with Buruli ulcer before, during and after antibiotic treatment to evaluate its association with the clinical and bacteriological response to therapy. METHODS: Biopsies of M. ulcerans infected skin lesions were obtained from patients before, during and after antibiotic therapy. Lipids were extracted from the biopsies and concentration of mycolactone was assayed by mass spectrometry and a cytotoxicity assay and correlated with clinical and bacteriological response to therapy. RESULTS: Baseline concentration of mycolactone measured by mass spectrometry predicted time to complete healing of small nodules and ulcers. Even though intra-lesional concentrations of mycolactone declined with antibiotic treatment, the toxin was still present after antibiotic treatment for 6 weeks and also 4 weeks after the end of treatment for 8 weeks in a subgroup of patients with slowly healing lesions. Additionally viable bacilli were detected in a proportion of these slowly healing lesions during and after treatment. CONCLUSIONS: Our findings indicate that baseline intra-lesional mycolactone concentration and its kinetics with antibiotic therapy are important prognostic determinants of clinical and bacteriological response to antibiotic treatment for Mycobacterium ulcerans disease. Mycolactone may be a useful biomarker with potential utility in optimising antibiotic therapy

Activity pacing: moving beyond taking breaks and slowing down

This brief communication responds to the paper by Jeong and Cho (Qual Life Res 26(4):903–911, 2017) that has described activity pacing in limited terms of adjusting activities through going at a slower rate and taking breaks. Activity pacing was reported as not involving goal setting, in comparison to other strategies for long-term conditions such as Acceptance and Commitment Therapy. This brief communication aims to challenge this limited perception of activity pacing in light of numerous studies that recognise pacing to be a more complex strategy. Pacing is considered to be a multifaceted coping strategy, including broad themes of not only adjusting activities, but also planning activities, having consistent activity levels, acceptance of current abilities and gradually increasing activities, and one that includes goal setting as a key facet. It is essential that pacing is both defined and measured as a multifaceted strategy in order to assess the outcomes of pacing, and for meaningful comparisons with other strategies regarding efficacy for the management of long-term conditions

Brain structural concomitants of resting state heart rate variability in the young and old: evidence from two independent samples

Previous research has shown associations between brain structure and resting state high-frequency heart rate variability (HF-HRV). Age affects both brain structure and HF-HRV. Therefore we sought to examine the relationship between brain structure and HF-HRV as a function of age. Data from two independent studies were used for the present analysis. Study 1 included 19 older adults (10 male, age range 62-78 years) and 19 younger adults (12 male, age range 19-37). Study 2 included 23 older adults (13 males; age range 55-75) and 27 younger adults (19 males; age range 18-34). The rootmean- square of successive R-R-interval differences (RMSSD) from ECG recordings was used as timedomain measure of HF-HRV. MRI scans were performed on a 3.0-T Siemens Magnetom Trio scanner. Cortical reconstruction and volumetric segmentation were performed with the Freesurfer image analysis suite, including 12 regions as regions-of-interests (ROI). Zero-order and partial correlations were used to assess the correlation of RMSSD with cortical thickness in selected ROIs. Lateral orbitofrontal cortex (OFC) cortical thickness was significantly associated with RMSSD. Further, both studies, in line with previous research, showed correlations between RMSSD and anterior cingulate cortex (ACC) cortical thickness. Meta-analysis on adjusted correlation coefficients from individual studies confirmed an association of RMSSD with the left rostral ACC and the left lateral OFC. Future longitudinal studies are necessary to trace individual trajectories in the association of HRV and brain structure across aging